Major finding: Mean liver stiffness decreased by 4.1 kPa 12 or more months after patients achieved sustained virologic response to treatment, but did not significantly improve in patients who lacked SVR.

Data source: A systematic review and meta-analysis of 2,934 patients from 23 observational studies and one post hoc analysis of a randomized controlled trial.

Disclosures: One reviewer disclosed funding from the National Institutes of Health/National Library of Medicine. The reviewers reported having no conflicts of interest.

The current era of new-generation direct-acting antiviral agents have revolutionized the treatment landscape of chronic hepatitis C virus infection, providing short-duration, safe, and consistently effective regimens that achieve SVR or cure in nearly 100% of patients. While achieving SVR is important, even more important is the long-term impact of SVR and whether cure translates into outcomes such as improved mortality or a reduced risk of disease progression. Although improved mortality after SVR has been demonstrated, one of the main drivers of risk of disease progression is the severity of hepatic fibrosis.

Dr. Robert J. Wong

In the current meta-analysis, Singh et al. elegantly addressed a recurring question among patients and providers regarding the effectiveness of DAAs: Does achieving SVR actually lead to durable improvements in hepatic fibrosis? This is an especially critical question as sustained improvements in fibrosis would translate into a long-term reduction in disease progression. Among a total of 24 studies that included 2,934 chronic HCV patients, the authors observed significant improvements in hepatic fibrosis, as measured by transient elastography, with the greatest improvements seen among patients with baseline cirrhosis. Although it has been debated that some of the initial improvements in liver stiffness measurements may be more reflective of improvements in liver inflammation that may confound fibrosis assessment, what is most striking about this study is the durability of fibrosis improvement beyond the first year after treatment. Even beyond 1 year after completing HCV treatment, patients who achieved SVR had a 28% median reduction in liver stiffness. Although the findings of this study are expected, the rigorous and systematic method by which the authors conducted their work further adds to the indisputable evidence supporting the benefit of HCV treatment.

Robert J. Wong, MD, MS, is with the department of medicine and is director of research and education, division of gastroenterology and hepatology, Alameda Health System – Highland Hospital, Oakland, Calif. He has received a 2017-2019 Clinical Translational Research Award from AASLD, has received research funding from Gilead and AbbVie, and is on the speakers bureau of Gilead, Salix, and Bayer. He has also done consulting for and been an advisory board member for Gilead.

Mean liver stiffness fell by 4.1 kPa (kilopascals) (95% confidence interval, 3.3-4.9 kPa) 12 or more months after patients achieved sustained virologic response to treatment, but did not significantly change in patients who did not achieve SVR, reported Siddharth Singh, MD, of the University of San Diego, La Jolla, Calif., and his associates in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.038). The results were especially striking among patients who received direct-acting antiviral agents (DAAs) or who had high baseline levels of inflammation, the investigators added.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Based on these findings, about 47% of patients with advanced fibrosis or cirrhosis at baseline will drop below 9.5 kPa after achieving SVR, they reported. “With this decline in liver stiffness, it is conceivable that risk of liver-related complications would decrease, particularly in patients without cirrhosis,” they added. “Future research is warranted on the impact of magnitude and kinetics of decline in liver stiffness on improvement in liver-related outcomes.”

Eradicating HCV infection was known to decrease liver stiffness, but the magnitude of decline was not well understood. Therefore, the reviewers searched the literature through October 2016 for studies of HCV-infected adults who underwent liver stiffness measurement by vibration-controlled transient elastography before and at least once after completing HCV treatment. All studies also included data on median liver stiffness among patients who did and did not achieve SVR. The search identified 23 observational studies and one post hoc analysis of a randomized controlled trial, for a total of 2,934 patients, of whom 2,214 achieved SVR.

Among patients who achieved SVR, mean liver stiffness dropped by 2.4 kPa at the end of treatment (95% CI, 1.7-3.0 kPa), by 3.1 kPa 1-6 months later (95% CI, 1.6-4.7 kPa), and by 3.2 kPa 6-12 months after completing treatment (90% CI, 2.6-3.9 kPa). A year or more after finishing treatment, patients who achieved SVR had a 28% median decrease in liver stiffness (interquartile range, 22%-35%). However, liver stiffness did not significantly change among patients who did not achieve SVR, the reviewers reported.

Mean liver stiffness declined significantly more among patients who received DAAs (4.5 kPa) than among recipients of interferon-based regimens (2.6 kPa; P = .03). However, studies of DAAs included patients with greater liver stiffness at baseline, which could at least partially explain this discrepancy, the investigators said. Baseline cirrhosis also was associated with a greater decline in liver stiffness (mean, 5.1 kPa, vs. 2.8 kPa in patients without cirrhosis; P = .02), as was high baseline alanine aminotransferase level (P less than .01). Among patients whose baseline liver stiffness measurement exceeded 9.5 kPa, 47% had their liver stiffness drop to less than 9.5 kPa after achieving SVR.

Coinfection with HIV did not significantly alter the magnitude of decline in liver stiffness 6-12 months after treatment in patients who achieved SVR, the reviewers noted. “[Follow-up] assessment after SVR was relatively short; hence, long-term evolution of liver stiffness after antiviral therapy and impact of decline in liver stiffness on patient clinical outcomes could not be ascertained,” they wrote. The studies also did not consistently assess potential confounders such as nonalcoholic fatty liver disease, diabetes, and alcohol consumption.

One reviewer disclosed funding from the National Institutes of Health/National Library of Medicine. None had conflicts of interest.